Although the mucosa of the gastrointestinal tract is both the largest lymphoid organ and largest surface area of the body, information regarding the cellular responses of the gut-associated lymphoid tissues is limited. Particularly sparse is information on the role of mucosal macrophages in the immunologic, inflammatory, and defense reactions directed against enteric microorganisms and foreign antigens. Therefore, the goal os this laboratory has been to isolate and purify lamina propria macrophages and to characterize their function in vitro and in vivo. Using combination neutral protease digestion-density gradient sedimentation-counterflow centrifugal elutriation, we have isolated from the lamina propria of normal human mucosa cells that by FACS analysis and light and electron microscopy are 85% to 95% macrophages. These cells express accessory cell function for mitogen and antigen presentation to peripheral blood and lamina propria T cells. Although lamina propria macrophages were found to be incapable of chemotaxis, they likely amplify the mucosal inflammatory response through their ability to secrete the chemoattractant cytokine TGF-beta. Lamina propria macrophages also exhibit phagocytic activity for mucosal microorganisms such as C. albicans. These functions may facilitate the ability of lamina propria macrophages to mediate the mucosal inflammation associated with certain enteric diseases, such as cytomegalovirus colitis and H. pylori-associated chronic gastritis.